The purpose of this project is to investigate the biological basis of human longevity. Our major research approach has been an investigation of the biochemical and molecular genetic basis of the variations found in the aging rate observed in different mammalian species, particularly primate species. Specific research projects have centered on testing the dysdifferentiative hypothesis of aging, where molecular genetic techniques are used to determine possible age-dependent alterations in gene regulation. Recent work has been centered on oncogenes. The possibility that active oxygen species may play a role in destabilizing proper gene regulation has been investigated by comparative measurements of oxidative stress in mammalian species of different maximum lifespan potential. This work involves measurements of antioxidant and DNA repair enzyme concentrations. Non-invasive assays of oxidative stress are also being developed. These assays include measurement of lipid peroxides and nucleic acid base damage production in serum and urine.